Roles and Heterogeneity of Mesenchymal Progenitors in Muscle Homeostasis, Hypertrophy, and Disease

Abstract

Skeletal muscle is mainly composed of multinucleated cells called myofibers and has excellent regenerative and adaptive abilities. These abilities are granted by muscle satellite cells (MuSCs), which are anatomically defined cells located between myofibers and basal lamina. In addition to myofibers and MuSCs, skeletal muscle contains several types of cells located in interstitial areas, such as mesenchymal progenitors. These cells are positive for platelet-derived growth factor receptor alpha and are called fibro/adipogenic progenitors (FAPs) or mesenchymal stromal cells. Although mesenchymal progenitors were originally identified as the causative cells of ectopic fat accumulation in skeletal muscles, recent studies have shed light on their beneficial roles in homeostasis, regeneration, and hypertrophy. Furthermore, the heterogeneity of mesenchymal progenitors is of great interest in understanding skeletal muscle development, homeostasis, regeneration, aging, and diseases. In this concise review, we summarize recent findings on the physiological roles of mesenchymal progenitors and their heterogeneity and discuss the remaining critical concerns.